The mechanism of nerve excitation was studied from a macromolecular viewpoint. The birefringent signals associated with an action potential in a dye-loaded squid giant axon was studied and found to be much larger than that obtained from an intact axon. The mechanical changes associated with the production of action potentials were studied using three different methods. All three methods yielded consistent results indicating the occurrence of swelling of nerve fibers associated with an action potential. In addition to this swelling, nerve fibers were found to undergo a transient shortening in their length during an action potential. The magnitude of this shortening was found to be 5-10 mn and the tension developed, 15-20 micrograms. These findings suggest that cytoskeletal structures associated with the axolemma, are involved in the process of nerve excitation.